Abstract

Friday, November 18, 2016

The outlier

I met Jay
Willis in a support group for people in the early stage of early-onset
Alzheimer’s disease. I had already learned that this disease typically moves
slowly, so it was no surprise that most of my cohorts remained articulate. But
Jay, a former lawyer, is particularly well-spoken. Recently, he left our
support group, but not because his condition was going downhill. Jay concluded
that he had stopped getting worse. Most remarkably, I learned that he was
diagnosed with the disease roughly fourteen years. The Alzheimer’s Association
website notes that it is possible to live for up to twenty years after being
diagnosed, but the assumption is that the person would be just a shadow of his
or her former self. Jay, in contrast, no longer shows any symptoms of the
disease at all. Is Jay a statistical freak? He says that the people at Brigham
and Women’s Hospital, where he has taken part in many clinical trials over the
years, nicknamed him “The Anomaly.”

Back in 1999, Jay was diagnosed with clinical depression.
He recalled, “I didn’t know what was going on. Just that every day I was waking
up and thinking, ‘Well, maybe I’ll die today and I won’t have to deal with
this.’” Depression, he discovered, can be an early sign of Alzheimer’s. In
2002, he was diagnosed with mild cognitive impairment, often a precursor to
Alzheimer’s. Jay was devastated. He had a prosperous law practice and what he
described as a photographic memory. But then he began forgetting things. Alzheimer’s
runs on both sides of his family, so he knew that he was at risk. Over the next
four years, his weight ballooned from a trim 190 pounds on his six-foot-two
frame to 245.

“My brothers and sisters thought I was faking, and I was
also regressing,” Jay recalled. “I didn’t know what was going on, either. Just
that every day I was waking up and thinking, ‘Well, maybe I’ll die today and I won’t
have to deal with this.’” Jay’s doctor advised him to close down his law
practice, and when Jay asked how soon, the answer was, “immediately.” It took a
year and a half to wind things down.

Over the years, Jay has aggressively sought out participation
in clinical trials, in the hope that he could reap the benefits of the drug
candidates before they received FDA approval. His earliest clinical trials came
soon after his diagnosis. At that time, some researchers thought that the first
symptoms of Alzheimer’s could be detected through the hippocampus, the seat of
short-term memory, which in cases of Alzheimer’s is typically the first part of
the brain to experience decline.

One of Jay’s earliest clinical trials was under the
direction of the Alzheimer’s researcher Dr. Dennis Selkoe at Brigham and
Women’s. In Jay’s view, if he had to walk the path of the disease, someone else
should learn something from it. About five years ago, Jay qualified for a modest
drug trial with roughly 200 participants. By then, he was much more social, his
depression long behind him. Dr. Selkoe didn’t think Jay would score low enough
to qualify for the trial, but in fact he did. “I continued to function, in
spite of this chemical imbalance in my brain,” Jay said. “Over the next two
years, I kept feeling better and better.” At the end of the five years, they
terminated the study.

Are there lessons to be drawn from Jay’s long experience
with Alzheimer’s? As one doctor of his said, “You should be mildly demented but
you’re not.” Jay’s experience is highly atypical, of course, if not downright
freakish. But one practice of his—intense aerobic exercise on a daily or
near-daily basis—is something that can benefit many of us who have the disease,
in the service of forestalling our way to our murky destination, a depot where
no one wants to arrive.